Orlistat

Orlistat, also known as tetrahydrolipstatin (THL), is a drug used to treat obesity in conjunction with a low-calorie, low-fat diet. The anti-obesity drug is used as a medical aid to lose weight (weight loss) and to maintain that weight afterwards (weight maintenance). It is classified within the drug class called lipase inhibitors, where lipase is produced primarily in the pancreas. Orlistat is a crystalline power that is whitish in color. Chemically, it is the saturated derivative of lipstatin, which is isolated from Streptomyces toxytricini. The empirical chemical formula for orlistat is C29H53NO5.

The drug orlistat was approved by the U.S. Food and Drug Administration (FDA) in 1999 for use within the United States. It was recommended for obese people with a body mass index (BMI) of more than 30 kilograms per square meters. It was also recommended when peoples’ BMI was between 27 and 30 kilograms per square meters and other heath considerations such as high blood pressure, elevated blood cholesterol, or diabetes were detrimental to their lives. Medical studies, which paralleled previous conclusions, performed before orlistat was approved by the FDA found that when taken for six months, adults lost 12.4 to 13.4 pounds on average. Orlistat is marketed under the prescription name Xenical® and the over-the-counter name alli®.

Orlistat prevents the digestion and absorption of dietary fats into the bloodstream so that, instead, they pass through bowel movements within the feces. Consequently, they reduce the amount of calories that go into the human body. It is often used within a physician-supervised diet plan for obese people and as a maintenance plan for formerly obese people after they have lost weight. It is also used for people desiring to lose weight when they have such illnesses as diabetes, high cholesterol, heart disease, or high blood pressure.

KEY TERMS

Bulimia—An eating disorder that involves cycles of overeating and undereating.

Cardiovascular disease—Diseases that have to do with the heart and blood vessels (veins and arteries).

Gastrointestinal—Relating to the stomach and intestines.

Hypertension—Disease of the arteries that usually indicate high blood pressure.

Immunosuppressant—Suppression of the immune system.

Lipase—An enzyme produced from the pancreas that breaks down fats.

Inside the human body, orlistat diminishes the production of pancreatic lipase, which is an enzyme that decomposes triglycerides within the intestines. When pancreatic lipase is not present, triglycerides which are ingested within foods, are stopped from being hydrolyzed into free fatty acids. They are, instead, excreted through bowel movements within feces without being digested. Orlistat, itself, is only slightly absorbed into the body. Most of it is taken into the gastrointestinal tract and eventually removed through the feces.

Orlistat was introduced into the marketplace primarily because of the increasing number of overweight or obese people in the United States and other countries around the world. According to the National Institutes of Health (NIH), as of 2007, about 65% of all U.S. adults are overweight or obese. NIH scientists have shown that being overweight or obese can lead to increased risk of developing health issues such as high blood pressure, heart disease, arterial disease, and type-2 diabetes. According to the World Health Organization (WHO), over one billion adults are overweight in the world, and at least 300 million of them are considered obese.

Orlistat is usually prescribed by medical professionals in a dosage of 120 milligrams three times per day, specifically after or during main meals. According to The Obesity Society, taking more than three dosages in one day has been shown ineffective at eliminating additional weight and, thus, is not recommended by medical doctors. Orlistat is available in a capsule that is taken orally (by mouth) during or up to one hour after the eating of main meals. It should be taken with a full glass of water.

According to the Mayo Clinic, these primary meals should contain no more than about 30% of fat by total calories. When used within these guidelines, about 30% of dietary fat is stopped from being absorbed into the body and, instead, is expelled through the feces.

The effectiveness of orlistat and, thus, the amount of weight loss achieved varies among humans. Orlistat, as of 2006, has been the most studied weight-loss medication on the international market. It has been used since 1999 in the United States and since 1998 in 145 other countries. Over 125 million people have used orlistat and more than 100 clinical studies with over 30,000 subjects have been performed. In all, it has been proved safe and efficient when used as prescribed.

A landmark one-year study, which concluded in 2007, was conducted by Xenical Pharmacology. The study shows that the drug reduces body mass by 5% or more in about one-third to one-half of the subjects and decreases body mass by at least 10% in about one-sixth to one-fourth of patients. The effectiveness and safety of orlistat have only been proven in four years or less of use.

Some side effects caused by the use of ortistat include gastrointestinal problems. Most problems reported happen within the first year of use, with the severity and number of problems diminishing over time. Because dietary fat is expelled with the feces, the stool may become oily, fatty, or loose. The color may change to an orange color. In addition, increased gas (flatulence) with noticeable discharge is frequently reported. Bowel movements are also more frequent and sometimes urgently sensed. It may become difficult to control bowel movements. Upon stopping the use of ortistat, feces return to normal fatty levels and color between 24 and 72 hours.

To minimize side effects, foods with a high fat content should be avoided. Physicians recommend a low-fat, reduced-calorie diet when taking ortistat. In addition, a well balanced diet should consist of even proportions of carbohydrates, fat, and protein that are distributed throughout one day over three large meals. If a main meal is missed or contains no fat, the pill can be eliminated, too. It is recommended that whole-milk products be replaced with nonfat milk or 1% milk and low-fat or reduced-fat dairy items. Baked items and prepackaged, processed, and fast foods should be avoided because they are usually high in fat content. In general, people taking orlistat should actively read food labels before buying and eating in order to avoid foods high in fat.

Because orlistat can impair the absorption of vitamins (especially A, D, E. and beta-carotene, which are classified as fat-soluble vitamins) and other nutrients into the body, a multivitamin should be taken daily, at least two hours before or several hours after taking ortistat, or at bedtime.

Problems with interactions may arise if orlistat is taken along with anticoagulants (blood thinners) such as warfarin (Coumadin®). A physician should monitor patients who are taking both drugs. Orlistat can also cause problems with diabetic medicines such as glipizide (Glucotrol®), glyburide (DiaBeta®, Dynase®, Micronase®), metformin (Glucophage®, Diabex®, Fortamet®), and insulin. Diabetics should consult with their doctor because the amount of oral diabetic medicine may need to be changed when weight loss has occurred.

Orlistat can also reduce the effectiveness of cyclosporine while being taken as an immunosuppressant drug to reduce the body’s risk of organ rejection after transplants. Make sure that cyclosporine is taken at least two hours before or after the taking of orlistat. The drug can also increase the absorption of pravastatin (Pravachol®, Selektine®), which is used to improve cholesterol levels and to prevent cardiovascular diseases.

The drug ortistat can also cause problems if other medicines for weight loss are taken along with the drug. According to the NIH, always consult with a medical physician before taking orlistat and to inform your doctor of any currently used medicines or allergic reactions (such as with animals, foods, dyes, or preservatives) before starting ortistat. Pregnant and nursing women should not take orlistat. Anyone with problems with an eating disorder, gallbladder, malabsorption syndrome (difficulty absorbing food), or kidney stones should not take orlistat.

The use of orlistat has been shown to increase the risk of breast cancer and colon cancer. However, such medical claims are preliminary in nature and further scientific research is necessary. Orlistat has also been shown to increase the risk for problems with the gallbladder and kidneys, along with complications in pregnancies and breastfeeding. It may cause complications if patients have problems with anorexia nervosa or bulimia, and thyroid disease.

According to the Mayo Clinic, orlistat has only been tested on adults. Information is not currently available on how children are affected by orlistat. In addition, studies performed on pregnant animals do not show evidence of harm to fetuses. However, according to the Mayo Clinic, orlistat is not recommended for pregnant women. Also, due to lack of medical studies, it is not recommended for women who are nursing newborn babies. Proper dosage amounts for children have not been determined. When considering the use of orlistat for children, a medical professional should be consulted as to the amount given for each individual child.

On February 7, 2007, the FDA approved Alli® as an over-the-counter drug. Alli® is a lower dose version (60 milligrams) of the prescription drug Xenical®. Made by GlaxoSmithKline PLC, it is the first weight loss drug to be approved for over-the-counter (OTC) use. Partially due to controversy with its release, when buying Alli® the package also includes Welcome and Companion Guides, a Calorie and Fat Counter, Quick Fact Cards, a Guide to Healthy Eating, a Daily Journal, and free access to an online action program. The company recommends Alli® only to people over the age of 18 years. Consumer advocacy organizations, such as Public Citizen, opposed the easy availability of Alli® as being potentially dangerous to the health of consumers.